[Analysis of dopamine transporter knockout mice as an animal model of AD/HD].

Abstract

Attention deficit/hyperactivity disorder (AD/HD) is characterized by significant difficulties of inattention and/or hyperactivity and impulsiveness. Dopamine transporter (DAT) knockout (KO) mice have been suggested to constitute an animal model of AD/HD. DAT KO mice exhibit persistently and profoundly elevated extracellular dopamine levels in the striatum and nucleus accumbens. These mice display numerous behavioral alterations that model aspects of AD/HD that include hyperactivity in novel environments and impulsivity. Both hyperactivity and impulsivity can be ameliorated by treatment with methylphenidate and nisoxetine. These drugs increase extracellular dopamine and norepinephrine levels in the prefrontal cortex. It is likely that methylphenidate and nisoxetine activate the prefrontal catecholamine systems by blocking the norepinephrine transporter (NET) function, thereby helping to improve AD/HD-like behavior in DAT KO mice.